The present invention relates to formulations for lipid vesicles and methods of their manufacture. More particularly, the present invention discloses paucimellar lipid vesicles designed of materials which have exceptional properties for cosmetic, edible, dermatological, and pharmaceutical use. The paucimellar vesicles have 2-10 lipid bilayers surrounding a large amorphous central cavity which can contain a water-immiscible oily material or an aqueous solution. These lipid vesicles have a combination of propylene glycol stearate and at least one other compatible amphiphile as the primary structural material of their lipid bilayers.
Lipid vesicles are substantially spherical structures made of amphiphiles, e.g., surfactants or phospholipids. The lipids of these spherical vesicles are generally organized in the form of lipid bilayers, e.g., multiple onion-like shells of lipid bilayers which encompass an aqueous volume between the bilayers. Paucilamellar lipid vesicles have 2-10 peripheral bilayers which surround a large, unstructured central cavity.
Until recently, liposome technology has been concerned mostly with vesicles composed of phospholipids. This is primarily because phospholipids are the principal structural components of natural membranes and, accordingly, lipid vesicles have been used as a model system for studying natural membranes. However, there are a number of problems associated with using phospholipids as synthetic membranes. Biological membranes are stabilized by membrane proteins and maintained by extensive enzymatic "support" systems that rapidly turn over, exchange or modify membrane lipids. Neither membrane proteins nor the requisite enzymatic support systems can be practically incorporated into the wall structure of liposomes, making the structures inherently less stable than natural membranes. In addition, the biological environment contains several potent phospholipases that rapidly break down free phospholipids. These phospholipids will attack liposomes and degrade the membrane. For these reasons, phospholipid liposomes placed in an in vivo environment are rapidly degraded.
Moreover, phospholipid liposome technology has other problems. Phospholipids are labile and expensive to purify or synthesize. In addition, classic phospholipid liposomes are in the form of multilamellar as opposed to paucilamellar vesicles and have poor carrying capacities, especially for lipophilic materials, and have poor shelf lives unless lyophilized in the dark with antioxidants. Finally, phospholipids degrade too rapidly in vivo for most pharmaceutical or vaccine applications.
For these reasons, there is increasing interest in liposomes made of commercially available nonphospholipid amphiphiles (see, e.g., U.S. Pat. No. 4,217,344, U.S Pat. No. 4,917,951, and U.S. Pat. No. 4,911,928). These molecules have a hydrophilic head group attached to a hydrophobic "tail" and are derived from long chain fatty acids, long chain alcohol's and their derivatives, long chain amines, and polyol sphingo- and glycerolipids. Commercially available amphiphile surfactants include, for example, the BRIJ family of polyoxyethylene fatty ethers, the SPAN sorbitan fatty acid esters, and the TWEEN polyoxyehtylene derivatives of sorbitan fatty acid esters, all available from ICI Americas, Inc. of Wilmington, Del. Paucilamellar vesicles comprised of such amphiphiles provide a high carrying capacity for water-soluble and water immiscible substances. The high capacity for water immiscible substances represents a unique advantage over classical phospholipid multilamellar liposomes.
Many cosmetic and dermatological preparations commonly include amphiphiles such as propylene glycol stearate, stearyl alcohol, polyoxyethylene fatty ethers (i.e., POE 10 stearyl alcohol), sorbitan fatty acid esters, and polyoxyethylene derivatives of sorbitan fatty acid esters (i.e., POE 20 sorbitan monostearate). These additives can be used as emulsifiers or thickeners, providing the "feel" to certain cosmetics and/or dermatologicals. Many of these additives also fall under the GRAS list of edible materials, and those that do not fall under the GRAS list are still likely to be non-toxic and ingestible. These additives can therefore be used in many food and pharmaceutical products. Consequently, it would be advantageous to use these additives as the lipid vesicle formers.
Accordingly, an object of the present invention is to provide a method of making paucimellar lipid vesicles using as a primary structural lipids of the bilayers amphiphiles which are commonly used in cosmetics, dermatologicals and pharmaceuticals.
Another object of the invention is to provide paucilamellar lipid vesicles which contain propylene glycol stearate and at least one other amphiphile as the structural lipids of the bilayers.
A further object of the invention is to provide a method of producing paucimellar lipid vesicles which readily encapsulate water immiscible oily materials and are manufactured from relatively inexpensive materials.
These and other objects and features of the invention will be apparent from the following description and the claims.